Chemotherapy is one of the commonly used methods for tumor treatment, but the occurrence of multidrug resistance (MDR) in tumors has added great difficulties for tumor treatment, causing serious harm to patients′ physiology and psychology. At present, there is a relative lack of research and treatment on tumor resistance in clinical practice, and finding reversal agents and strategies for tumor resistance is an urgent problem to be solved. This article reviews the mechanism of tumor multidrug resistance and its reversal methods and research status of Chinese medicine as reverse agent, aiming to provide reference for future research.

OBJECTIVE To evaluate the microbial contamination levels of 14 kinds of mold-prone TCM decoction pieces and the diversity of fungi on the surface. METHODS The total aerobic microbial count (TAMC), total yeasts and molds count (TYMC), heat-resistant microbial count (HRMC), and three types of control bacteria of mold-prone TCM decoction pieces were analyzed by referring the Chinese Pharmacopoeia 2020 Edition Volume Ⅳ 1108 microbiological limit test method. Furthermore, the fungi on the surface were cultivated using the plate method, and the single strain was isolated by the top purification method, which was further identified by colony morphology and molecular identification. RESULTS The results showed that TAMC of sample ranged 250-2.45×10⁶ cfu·g^-1, TYMC ranged 5-6.6×10⁵ cfu·g^-1, and HRMC ranged 0-30 cfu·g^-1. The remaining samples of cholesterol-resistant progestin-negative bacteria did not reach 1×10⁴ cfu·g^-1, with the exception of one batch of Polygalae Radix and one batch of Glycyrrhizae Radix et Rhizoma. Although only one batch of Citri Reticulatae Pericarpium tested Escherichia coli and no Salmonella was detected in all samples, significant conditional pathogenic bacteria such as Enterobacter cloacae, Klebsiella pneumoniae, and Cronobacter sakazakii were found in the control bacterial examination items. ITS sequence sequencing comparison identified 106 strains in total, grouped into 16 genera, with Aspergillus, Penicillium, and Cladosporium accounting for 31%, 18%, and 17%, respectively, of the major bacteria. Among the genus Aspergillus, 11 strains of A. niger, 7 strains of A. flavus, 2 strains of A. fumigatus, and 1 strain of A. miscellaneous were isolated as pathogenic fungi. CONCLUSION It can provide early risk warning for its potential fungi toxins contamination through research on microbial pollution and surface fungi diversity.

OBJECTIVE To investigate the effects of carbohydrate components of fungus S7 (Tulasnella sp.) on seed germination of Dendrobium officinale. METHODS The polysaccharides of S7 mycelia (MP) and of S7 fermentation broth (FP) were prepared by water extraction and alcohol precipitation. MP and FP were hydrolyzed by trifluoroacetic acid to obtain hydrolysates, MPH and FPH. The monosaccharide composition of MP and FP were determined by PMP-HPLC. MP, FP, MPH, FPH, and the unique and mixed monosaccharide of MP were added to water agar (WA) and 1/2 MS media respectively to study the effects of carbohydrate on the seed germination of Dendrobium officinale. RESULTS The germination rate of WA medium group (WACK1) was (88.65±4.71)%, and seeds germinated to stage 3 (protocorm). Compared with WACK1, adding MP and MPH had no significant effect on germination rate (P>0.05), and seeds could germinate to stage 4 (having one leaf), while adding FPH could significantly reduce germination rate (P<0.05). MP was composed of glucose, galactose, glucuronic acid, xylose, mannose, fucose, ribose and arabinose in a molar ratio of 15.05∶1.00∶0.70∶0.35∶0.30∶0.29∶0.13∶0.13. FP was composed of arabinose, galactose, xylose and glucuronic acid in a molar ration of 1.22∶1.00∶0.71∶0.47. Fucose was the unique monosaccharide component of MP. The germination rate and stage 5 (having two leaves) germination rate of 1/2 MS medium group(MSCK) was (98.10±0.46)% and (50.97±4.33)%, respectively. Compared with MSCK, adding 0.20-20 mg·L^-1 fucose had no significant effect on germination rate (P>0.05), while significantly increased stage 5 germination rate (P<0.05), which was 1.36-1.47 times that of MSCK. CONCLUSION MP and MPH promote the development of protocorm of D.officinale. Fucose is an active component in MPH that could promote the further differentiation and development of seeds after germination.

OBJECTIVE To provide the basis for the original source and quality control, and investigate herbal textual and pharmacognosy of Yi medicine Peperomia tetraphylla(Guo Jiu Lu). METHODS By consulting ancient and modern herbal literature combined with actual investigation and research, the research was carried out from four aspects: name, the origin, Yi medicinal use history and folk proved prescription. The plant morphology and medicinal properties were observed and described, the paraffin sections of stems and leaves and the whole grass powder were prepared to observe the microscopic characteristics.Physicochemical identification was performed based on thin-layer chromatography.The content of α-asarone in P.Tetraphylla was determined by HPLC.The volatile oil was extracted by steam distillation and the volatile components were analyzed by GC-MS. RESULTS In different herbal works, the proper names recorded with Peperomia tetraphylla. as the original plant are not uniform, and there are many other names, including 5 proper names and 44 specific names. The phenomenon of the same substance with different names is very prominent. In addition, the foreign substance of the same name also exists objectively: in addition to the Piperaceae plant Peperomia tetraphylla., the drug recorded with the name of "Yizhuxiang" also involved the Rubidiaceae plant Hedyotis capituligera Hance. The related plants of Peperomia genus Peperomia blanda and Peperomia duclouxii were also known as Peperomia tetraphylla., which was a foreign substance of the same name. The medicinal use of Yi nationality could be traced back to the journal of《Yunnan Sheng Zhi》, comprehensive research, the yi language called: , transliteration name: Guo Jiu Lu. Ten folk empirical prescriptions were recorded in the literature. Systematic pharmacognostic study was carried out on 10 lots of collected medicinal materials, and the morphological characteristics, tissue structure, powder characteristics, and physical and chemical identification characteristics of the medicinal materials were determined. The content of α-asarone was determined by HPLC between 0.0648% and 0.5916%, the volatile oil of 5 batches of medicinal materials from Sichuan, Yunnan and Guizhou were analyzed by GC-MS, and 24 compounds were identified,and 5 compounds with relative percentage content greater than 2% were obtained by peak area percentage method. CONCLUSION This paper systematically completes the herbal research and pharmacognotic research of Yi medicine P.Tetraphylla, and promotes its inclusion in the 《Standard of Traditional Chinese Medicinal Materials in Sichuan Province》 (Tibetan, Yi, Qiang and Miao Medicinal Materials 2022 edition), which will provide an important basis for the scientific evaluation and in-depth development of the quality of P.Tetraphylla.

OBJECTIVE To study the effect of different particle size of nifedipine on the in vitro and in vivo equivalence of its sustained-release tablets (Ⅰ), and confirm the appropriate range. METHODS The effect of API with different particle size on the dissolution of nifedipine sustained-release tablets (Ⅰ) was evaluated by experimental design and dissolution similarity factors (f₂), and the in vitro dissolution and in vivo bioequivalence of the commercial products with the reference preparations were compared. RESULTS The dissolution of the industrial products prepared by micronizing the API to Dv90 ≤20 μm is similar to the reference preparations in four dissolution media in vitro, and both are bioequivalent in vivo. CONCLUSION The particle size of API is the key factor affecting the release and equivalence of nifedipine sustained-release tablets (Ⅰ).

OBJECTIVE To study the in vivo pharmacodynamics of paclitaxel-loaded TPGS-modified carboxymethyl chitosan-rhein conjugate micelles (PTX/TPGS-CR micelles) in tumor-bearing mice. METHODS The pH and osmotic pressure value of PTX/TPGS-CR micelles were determined. The 4T1 subcutaneous transplanted tumor model was established in Balb/c mice. Taxol^® was used as the positive control, and the tumor growth curve and tumor inhibition rate were used as the main indicators. The safety and efficacy of PTX/TPGS-CR micelles were investigated by observing the changes in body weight, organ index and pathological tissue sections of mice, and measuring the expression of P-gp protein in tumor tissues of each group. RESULTS The pH value was similar to that of 0.9% sodium chloride injection (5.0-7.0), and the osmotic pressure value was 736.6-757.2 kPa. The tumor inhibition rates of Taxol^® and PTX/TPGS-CR micelle in low, medium and high dose groups were 29.91%, 20.87%, 41.06% and 41.84%, respectively. The antitumor effect of PTX/TPGS-CR micelles was better than that of Taxol^® at the same dose (P<0.05), and showed a dose-dependent feature. During the administration period, the body weight and organ of the mice in the PTX/TPGS-CR micelle group at the same dose showed no significantly affected, indicating that PTX/TPGS-CR micelles had better safety. The results of P-gp expression in tumor tissue showed that TPGS-CR micelles could inhibit the expression of P-gp protein. CONCLUSION PTX/TPGS-CR micelle preparation is a nano preparation with high efficiency and low toxicity. It has a good antitumor effect and can reduce the toxicity of PTX. Moreover, it can improve the sensitivity of tumor cells to PTX by inhibiting the expression of P-gp, which is conducive to the treatment of tumors.

OBJECTIVE To analyze the impurity profile of irbesartan and its preparations by LC-MS/MS. METHODS ZORBAX SB-C₁₈ column (4.6 mm×150 mm, 3.5 μm) was used for the separation of the related substances with a mixture of 0.1% formic acid solution (adjusted to pH 3.5 with ammonia) and acetonitrile (62∶38) as the mobile phase by isocratic elution. The structures of the related substances were speculated by ESI-TOF-MS/MS and verified further by reference substances. RESULTS Irbesartan and its related substances were separated under the established chromatographic condition, and a total of 16 related substances were detected. The structures of 10 related substances were verified by reference substances. CONCLUSION The established LC-MS/MS method is effective for separation and identification of the related substances of irbesartan and its preparations, and the results obtained are valuable for its quality control and manufacturing process.

OBJECTIVE To study the factors affecting the generation of the degradation impurity 2-[(4-acetylphenyl)methyl]cyclopentanone (loxoprofen sodium impurityⅠ) in loxoprofen sodium tablets thus to provide reference for the formulation, preparation process and packaging design of loxoprofen sodium tablets. METHODS Stress testing of loxoprofen sodium and loxoprofen sodium tablets were carried out in conditions of high temperature (60 ℃), high humidity (92.5% RH) and strong light irradiation (4 500 lx). The compatibility test of loxoprofen sodium with excipients, and the content of impurity Ⅰ in bare tablets and different packages of loxoprofen sodium tablets were investigated under accelerated test conditions (50 ℃ and 75% RH). The content of impurity Ⅰ was determined by HPLC. RESULTS Loxoprofen sodium impurity Ⅰ is sensitive to humidity. High water content, moisture attracting and hydrophilic excipients such as calcium hydrogen phosphate, silicon dioxide and sodium starch glycolate might cause a significant increase of impurity Ⅰ. Moreover, there was incompatibility between mannitol and loxoprofen sodium, and the sealing performance of the package of aluminum plastic plate plus aluminum foil bag was better than that of the aluminum plastic plate package alone. CONCLUSION In order to reduce the generation of potentially toxic impurity Ⅰ, the excipients of loxoprofen sodium tablets and the granulation after drying should be controlled for water content. The use of aluminum plastic plate plus aluminum foil bag with better sealing performance can effectively reduce the generation of impurity Ⅰ. In addition, mannitol and loxoprofen sodium have compatibility problems and should be avoided in the prescription.

OBJECTIVE To analyze the characteristics of methylphenidate (MPH) related treatment emergent adverse events (TEAE) in children, so as to provide recommendations for prevention of MPH safety events. METHODS Case reports of MPH-induced TEAE in children were retrieved from CNKI, VIP, Wan Fang, PubMed, Web of Science, EMbase and other databases, and the gender, age, dosage, drug combination, time of adverse reactions and clinical manifestations of the patients were statistically analyzed. RESULTS A total of 39 case reports were collected, involving 50 cases, including 47 cases in the treatment group and 3 cases in the non-treatment group. In the treatment group, the ratio of male to female was 3.7∶1, with 40 cases (80%) in patients aged 6-15 years. Most TEAEs occurred within 1-30 d after drug administration (32 cases, 64%), and the TEAEs mainly involved mental system (12 cases, 21.43%) and nervous system (11 cases, 19.64%). In the non-treatment group, 2 patients were overdosed, and adverse reactions occurred within 1 h, mainly involving mental system and nervous system. Among the 50 cases, 49 cases were improved after drug withdrawal and/or symptomatic treatment, and 1 case had unknown prognosis. CONCLUSION It is necessary to prevent the possible safety problems in the use of MPH, so as to improve the level of rational drug use.

OBJECTIVE To analyze the characteristics of clinical pharmacists′ participation in consultation cases of infectious diseasesin the intensive care unit (ICU), summarize the experience and effect and provide reference for promoting the rational use of antiinfection drugs in ICU. METHODS A retrospective analysis was conducted on the cases of clinical pharmacists participating in ICU infection consultation from November 2021 to MAY 2023, and the basic data, common etiology, consultation purpose, adoption rate, and prognosis of these cases were statistically summarized. RESULTS Among the 72 consultations, there were 60 patients with positive etiological examination results and 73 strains of virus, including 35 strains of Gram negative bacteria, 28 strains of Gram positive bacteria, and 10 strains of fungi. The top three bacteria were Pseudomonas aeruginosa (23.61%), Staphylococcus aureus (16.67%), and Klebsiella pneumoniae (9.72%). The top three clinical consultation purposes were the selection of antibacterial drugs for positive bacterial/fungal culture (47.22%), the adjustment of medication due to poor early protocol (22.22%), and the selection of antibacterial drugs for specific site infections (12.50%). The top three consultation opinions given by pharmacists were 24 cases of adjusting the type of antibacterial drugs, 16 cases of adding antibacterial drugs, and 16 cases of continuing the original antiinfection treatment plan. The consultation opinions were adopted in 62 cases and not adopted in 10 cases, with an adoption rate of 86.11%. Among them, the treatment effectiveness rate of patients with accepted opinions was 74.19%, and that of patients without accepted opinions was 30.00%. The prognosis of patients with accepted opinions was better (P<0.05). CONCLUSION Due to the particularity of ICU patients and the limitation of drug selection, antiinfection treatment is difficult. Clinical pharmacists participate in consultation of ICU infected patients and formulate drug treatment plans can improve the cure rate of infectious diseases, which is of great significance to promote the rational use of antibiotics and improve the prognosis of patients.

OBJECTIVE To discuss the risk management methodology of data integrity implementation in drug quality control laboratories. METHODS The regulations and guidelines for data integrity were interpreted. How to apply quality risk management in data management was discussed, and combining the practical experience of laboratory, how to implement data integrity work in drug quality control laboratories through risk management was proposed. The focus was to systematically identify and map the processes, data flows, and systems of the laboratory based on the data life cycle, and analyze the gap between the current data management status and the regulation requirements. Then, using the risk management tools of ICH Q9, risk evaluation, control, and review need to be conducted to form a closed-loop risk management to control the data integrity risk within an acceptable range. RESULTS AND CONCLUSION Drug quality control laboratories should implement data management based on quality risk management principles. The implementation method proposed in this article can comprehensively evaluate and control the data integrity risks of the laboratory, which has strong practicality and can be used as a reference for other drug quality control laboratories.